Growth failure and hormone therapy.

Growth failure and hormone therapy One of the causes of growth failure is growth hormone deficiency. The outcome of growth hormone therapy to treat this depends on a number of multifaceted issues, including the child, the family and the choice of medication device. Providing support and promoting adherence—key nurse roles—are essential for success Peter Laing Advanced Paediatric Nurse Practitioner, Endocrinology, Alder Hey Children’s NHS Foundation Trust

M

ost children with short stature are essentially healthy, although growth can also be a sensitive indicator of a child’s general health and wellbeing. Monitoring growth is important in the early detection of disease, especially a wide variety of endocrine abnormalities in which poor growth may be the earliest or only sign of a clinical problem (Drake and Kelnar, 2006).

Growth failure

Growth disorders can result from irregularities in genes, hormones, nutrients and environmental factors, such as psychosocial deprivation, at any point during the first two decades of human life. These disorders are the most common problems experienced in paediatric endocrinology (Chernausek, 2009); however, growth hormone deficiency or other endocrine conditions account for only a small percentage of children affected (Wales, 2009). Causes of short stature are listed in Table 1. Childhood growth is the product of a complex interaction of nutrient supply (above that required for basic metabolism) and hormones acting on growth plates in the bones (Box 1), with surplus energy being converted into muscle or deposited as fat. Such a process is easily disrupted and can serve as a marker for conditions such as coeliac disease and chronic renal failure, and environmental issues, as described above (Wales, 2009). There are four distinct phases of human growth, each of which has different predominating control mechanisms: {{ Foetal {{ Infantile {{ Childhood {{ Pubertal.

Growth hormone therapy supplement

Table 1. Causes of short stature Non-pathological

{{ Constitutional delay of growth and puberty {{ Familial short stature {{ Nutritional issues {{ Emotional deprivation {{ Intrauterine growth retardation

Intrauterine growth retardation/restriction

{{ Syndromes – including Russell Silver syndrome {{ Non-syndromic

Systemic disorders

{{ Cardiovascular disease {{ Renal, including chronic renal failure {{ Respiratory, including asthma and cystic fibrosis {{ Gastrointestinal, including inflammatory bowel disease, Crohn’s, coeliac disease {{ Neurological {{ Psychosocial, including anorexia, child abuse and neglect

Endocrine causes

{{ Growth hormone-related causes {{ Growth hormone deficiency, isolated or combined with multiple pituitary hormone deficiency {{ Growth hormone resistance {{ Hypothyroidism {{ Cushing’s syndrome {{ Exogenous steroid administration and glucocorticoid excess

Chromosomal and genetic causes

{{ Turner syndrome {{ Noonan syndrome {{ Down’s syndrome {{ Skeletal dysplasia {{ Prader-Willi syndrome

S3

Journal of Nursing. Downloaded from magonlinelibrary.com by 130.194.020.173 on November 25, 2015. For personal use only. No other uses without permission. . All rights re

Box 1. Bone anatomy

Growth plate (also known as epiphyseal plate) is hyaline cartilage found at the end of long bones, such as the femur and tibia. The plate is found in children and adolescents, and is replaced by the epiphyseal line in adults.

_

Hypothalamus

+

with their peers, and those with skeletal dysplasias including achondroplasia and other constitutional disorders of bone.

Secondary growth failure

Secondary growth failure is related to insufficient nutrient intake (malnutrition) or malabsorption, and disorders in organ systems including respiratory, renal and cardiac. It is also associated with growth hormone deficiency and other endocrine disorders, as well as metabolic and psychosocial factors.

Idiopathic short stature _

GHRH +

IFC-I produced by the liver exerts negative feedback on GH secretion

Somatostatin _ Anterior Pituitary

GH

Growing bones +

+

Liver Epiphyseal growth plate IGF-I

Figure 1. Growth hormone secretion is controlled by the hypothalamic growth hormone-releasing hormone (GHRH) and somatostatin, which exert a stimulatory and inhibitory effect, respectively, on the pituitary gland. Insulin-like growth factor-1 (IGF-1) produced in the liver in response to growth hormone may operate in a negative feedback loop on the pituitary gland and hypothalamus. It exerts an anabolic effect in the body, with an increase in protein and collagen synthesis, leading to growth in bone and soft tissues Aberrations in growth can occur throughout these phases, and have a myriad of causes. The European Society of Paediatric Endocrinology (ESPE) identifies numerous factors affecting growth in its classification of paediatric endocrine diagnoses (Witt et al, 2007). ESPE groups these factors within three broad categories of diagnosis: {{ Primary growth failure {{ Secondary growth failure {{ Idiopathic short stature.

Primary growth failure

Primary growth failure is seen in a host of clinically defined syndromes including Turner syndrome, Noonan syndrome, Russell Silver syndrome and less commonly known syndromes. Primary growth failure is also associated with children who are born small for their gestational age who fail to catch up growth

S4

Causes of idiopathic short stature are well documented in the literature and are often related to familial or constitutional factors (the latter relates to the individual’s ‘make-up’).

Human growth

The four phases of human growth start at conception with the rapid proliferation of cell division in utero, with infant (aged over 1 month) growth viewed as an extension of the foetal growth phase. The rapid and early growth phase seen in height and weight during early infancy (from 1 month to 1 year) relies on adequate nutrition, thyroid function and bone metabolism. The hypothalamic-pituitary axis, where the hypothalamus gland in the brain stimulates the adjoining pituitary gland to release growth hormone, becomes increasingly active during late infancy, as growth during early childhood (from 2 years of age) becomes more dependent on growth hormone. This stimulates the liver to produce insulin-like growth factor-1 (IGF-1), which acts on the epiphyseal cartilage cells; IGF-1 is the major postnatal growth factor that stimulates cell division and growth (Whitehead and Miell, 2013). Puberty is associated with a distinct phase of increased growth and sexual maturity. It depends on the action of both growth hormone and sex hormones, leading to attainment of final adult height.

Growth hormone deficiency

Growth hormone deficiency is reported to affect one in 3500–4000 children (Lindsay et al, 1994). Human growth hormone (HGH), also known as somatotropin, is essential for normal growth in children; it is synthesised, stored and released by the somatotropic cells of the anterior pituitary gland (Dattani and Preece, 2004). The pituitary gland and hypothalamus are central regulators of growth, metabolism, development and reproduction. Growth hormone is synthesised and stored by cells in the anterior pituitary gland, which is located within the sella turcica at the base of the brain and is secreted in an intermittent and pulsatile pattern under the control of the hypothalamus.

British Journal of Nursing, Vol 23, No 6


This complex process results largely from to the interaction between growth-hormone-releasing hormone (GHRH) and growth-hormone-inhibiting hormone (also known as somatostatin). These are controlled and regulated by the hypothalamus, with peak serum growth hormone concentrations being achieved during sleep. These concentrations increase naturally during puberty, along with a rise in sex hormones, culminating in the pubertal growth ‘spurt’ and eventual cessation of growth and attainment of final adult height. The principal actions of growth hormone are to modulate somatic (body) growth by increasing chondrocyte proliferation and elongation at the epiphyseal growth plate (causing longitudinal bone growth) by stimulating IGF-1 generation in peripheral tissues, primarily the liver. Growth hormone also promotes the growth and development of muscle, bone and other tissue during maturation, and influences protein, lipid and carbohydrate metabolism throughout life (Figure 1).

Causes of childhood growth hormone deficiency

Growth hormone deficiency is the most common endocrine disorder associated with short stature (Kirk, 2012). It can be isolated, or combined and related to a more specific and wider constellation of hormone deficiencies, such as in multiple pituitary hormone deficiency. Growth hormone deficiency can be idiopathic, congenital, or acquired as a result of peri- or postnatal trauma, central nervous system infections and tumours affecting the hypothalamicpituitary region, most commonly craniopharyngioma (Dattani and Preece, 2004). Around 70% of patients (Dattani and Preece, 2004) have isolated growth hormone deficiency, which is idiopathic (Kirk, 2012). Table 2 lists some of the causes of childhood growth hormone deficiency.

Clinical signs of growth hormone deficiency

Growth hormone deficiency can present in the neonatal period as one element of panhypopituitarism (secretory deficiency of the pituitary gland) but the average age of diagnosis and treatment is 6–8 years (Ranke et al, 2007). The clinical features of growth hormone deficiency depend on whether it is congenital or acquired, and are related to short stature for parents, low height velocity, normal appearance of body proportions but larger head than height centile, small mid face (mid-facial hypoplasia), a high-pitched voice, truncal adiposity, delayed dentition and bone age (degree of maturation of a child’s bones) and delayed


Table 2. Causes of childhood growth hormone deficiency Genetic (eg, PIT 1) Idiopathic Congenital: structural defects

{{ Septo-optic dysplasia {{ Arachnoid cyst {{ Corpus callosum agenesis {{ Associated with midline defects

Acquired

{{ Peri- or postnatal trauma {{ CNS infections {{ Cranial irradiation {{ Tumours of the hypothalamus or pituitary regions {{ Craniopharyngioma {{ Glioma/astrocytoma {{ Germinoma {{ Lymphoma {{ Histiocytosis

puberty and small genitalia in boys (Wales, 2009). Hypoglycaemia can occur during early infancy or in the neonate with growth hormone deficiency (Drake and Kelnar, 2006). Congenital growth hormone deficiency is often due to a structural abnormality of the pituitary gland and is associated with medical conditions such as optic nerve hypoplasia or other midline defects that can be present from birth. Several genes are associated with hypopituitarism, including mutations identified in Prop-1 and HESX1 (Dattani, 2005; Dattani and Preece, 2004).

Testing for growth hormone deficiency

Given that growth hormone is normally secreted in a pulse-like manner, with most pulses occurring at night, random single measurements of growth hormone levels in the blood are rarely helpful in confirming or excluding a diagnosis of growth hormone deficiency. Diagnosis is therefore based initially on clinical presentation, with biochemical growth hormone stimulation tests carried out for confirmation. These use a pharmacological agent to release growth hormone into the peripheral circulation. The amount of growth hormone measured is a surrogate marker of the amount of hormone secreted by the pituitary gland. Agents used include glucagon, insulin, arginine, clonidine and GHRH. The evidence suggests that all have limitations in terms of their specificity and sensitivity (Wit et al, 2009; Wales, 2009). Growth hormone stimulation tests can be unpleasant for patients because of their side effects, which include nausea and vomiting, low blood glucose levels and hypotension (Stanhope, 1993).

S5


Despite this, guidance including that produced by National Institute of Health and Care Excellence (NICE, 2010) recommends that growth hormone stimulation tests should be carried out to biochemically support the clinical diagnosis of growth hormone deficiency. Tests are best performed in specialist paediatric centres by experienced staff using approved guidelines and protocols, as then any risk of subsequent morbidity will be extremely low. Patients with confirmed growth hormone deficiency may require radiological investigations, including magnetic resonance imaging, to establish the presence of any structural abnormality of the pituitary gland and possible identification of pituitary or hypothalamic lesions including tumours and midline defects of the brain.

Treatment

Since the mid-1980s, this has been in the form of recombinant human growth hormone (rHGH), somatropin (Fisher and Acerini, 2013). (Somatotropin is the chemical name for growth hormone and somatropin is the pharmaceutical name.) NICE (2010) has recommended that somatropin can be used to treat children with growth failure who have growth hormone deficiency, Turner syndrome, Prader-Willi syndrome, chronic renal insufficiency, short stature homeobox-containing gene deficiency (SHOX) (Box 2) and those born small for their gestational age with evidence of growth failure at 4 years of age or later.

Box 2. Conditions where growth failure can be treated with somatropin Turner syndrome

This affects females who have an incomplete or missing X chromosome. Its main features are short stature and underdeveloped ovaries, although other symptoms and characteristics can be present. It is often not diagnosed until puberty. It occurs in around one in 2000 live female births

Prader-Willi syndrome

This genetic condition has a wide range of symptoms, including an insatiable appetite, learning difficulties, behavioural problems, low muscle tone, motor development delays, incomplete sexual development and short stature. It affects one in every 15 000 live births in England

Short stature homeobox-containing gene deficiency (SHOX)

The short stature homeobox gene (SHOX) is one of several genes that control the formation of many body structures in early embryonic development. It is essential for skeletal development, particularly in the arms and legs. Defects in this gene are associated with growth retardation and the short stature of people with Turner syndrome

S6

The objectives of growth hormone therapy during childhood and adolescence are to normalise height velocity as quickly as possible and attain a final adult height within the normal target range, while also minimising the potential for side effects, such as headache, visual problems, nausea and vomiting, fluid retention (peripheral oedema), arthralgia, myalgia, carpal tunnel syndrome, paraesthesia, antibody formation, hypothyroidism and reactions at injection site (NICE, 2010), although these are relatively rare. Children with growth hormone deficiency who are treated with rHGH can experience excellent catch-up growth, but the success of treatment can be affected by variables such as birth weight, age at start of treatment, extent of growth hormone deficiency, duration of treatment, frequency of growth hormone injections, height at the start of treatment and height at the start of puberty. For example, patients who start taking growth hormone therapy too late (i.e. after their pubertal growth spurt) are likely to have a significantly short stature as adults. Other factors that can affect treatment outcomes include cancer, chemotherapy and radiotherapy and the concomitant use of other hormone replacement therapies including thyroxine, sex steroids and glucocorticoid replacement, which, based on the author’s clinical experience, influence growth in children with multiple pituitary hormone deficiency. Over the past decade, there has been an increase in the number of both growth hormone manufacturers and devices. In the UK, specialist endocrine units offer new patients some form of choice in devices for starting growth hormone therapy, although there are regional variations (Langham et al, 2011).

Factors affecting treatment with growth hormone

The success of growth hormone therapy depends on patients’ ability to adhere to their treatment regimen, and poor adherence with growth hormone therapy is frequently reported in children with growth hormone deficiency (Kapoor et al, 2008). The terms adherence, compliance and concordance are often used interchangeably in the literature, but they have different meanings (Bissonnette, 2008). Adherence refers to the patient’s medicine-taking behaviour. In contrast, concordance refers to the relationship between the patient and clinician, and is based on the view that they should work in partnership; this is in keeping with modern health-care ideology with patient empowerment, personal responsibility, choice, information sharing and informed decision making being central to functional engagement between patients and health-care professionals.




may be an influencing factor. Younger children or children with learning difficulties are often unaware of the need for treatment and can be reluctant for the growth hormone to be administered. In adolescence, additional barriers to adherence may include denial, lack of insight or interest in the medical condition, and factors relating to peer pressure or feeling different/isolated from peers. Other issues may relate to independence/lack of independence and potential conflict with the parent or carer, lack of independence over the medical condition and decisions regarding treatment, and lack of engagement with and trust in medical staff. The psychosocial and emotional demands of adolescence, combined with boredom, lack of interest or insight into the long-term effects and potential outcomes of treatment, and a preoccupation with other pursuits can affect adherence. This can result in ‘treatment fatigue’, which can also be related to the long-term nature of growth hormone therapy.

Promoting positive clinical outcomes

There is a need for effective interventions to improve adherence with growth hormone therapy, and a number have been proposed. Fisher and Acerini (2013) suggested that no single intervention, including giving patients choice over injection device, is likely to be effective in all cases. A holistic, patient-centred approach is required, with assessment starting before treatment begins and continuing throughout the duration of therapy, as needs and circumstances can often change. At present, seven equipotent brands of somatropin are available. Patient choice in terms of the growth

Will & Deni McIntyre/Science Photo Library

An extensive literature review suggested that adherence with growth hormone therapy in children and adolescents is variable and remains a problem, and can affect growth outcomes and future health, with associated economic consequences for the NHS (Haverkamp and Gasteyger, 2011). Generally, the presence of concomitant diseases, geographical location and prognosis appear to have little effect on adherence rates (Haynes et al, 2008). Several clinical studies have reported significant variation in adherence with growth hormone treatment, with 36–49% of patients saying they had adhered with treatment since their last clinic visit (Haverkamp and Gasteyger, 2011). This is supported by a recent systematic review on adherence with growth hormone therapy, with estimates of the prevalence of non-adherence varying from 5% to 82% (Fisher and Acerini, 2013). Adherence patterns change during the course of treatment, with teenagers having the lowest rates (Rosenfeld and Bakker, 2008). Further research suggests that adherence is generally best in adulthood and worst in adolescence, with intermediate rates in childhood (Fisher and Acerini, 2013). Kapoor et al (2008) objectively assessed adherence with growth hormone therapy and indicated that 17 of the 75 (23%) patients in their study missed more than two injections per week, and that lower adherence was significantly associated with longer duration of growth hormone therapy, lack of choice of growth hormone delivery, shorter prescription durations and a predicted lower height velocity. Non-adherence may also lead to additional diagnostic tests, repeated clinic attendance at hospital, unnecessary changes of drug dose and treatment course, and an increase in health-care costs, with poorer overall outcomes (Fisher and Acerini, 2013; Haverkamp et al, 2008). Barriers to adherence in paediatric patients include perceived ineffectiveness of treatment (as children may feel that their growth rate is too slow), concern about potential side effects and issues related to the scheduling of dose administration, given that the therapy is usually administered in the evening. Other factors can include cognitive and emotional issues, forgetfulness, preoccupation, lack of understanding of the condition, lack of symptoms, fear of needles and inadequate family support. Psychological and emotional factors, socioeconomic issues such as poverty, illiteracy, low levels of education, unemployment, deprivation and poor social support networks, cultural beliefs, and parental separation and the child’s resultant living arrangements all affect adherence (Fisher and Acerini, 2013; Haverkamp et al, 2008). The involvement of a third party or parties, including a parent/guardian, carer or other members of the child’s extended family,

Boy being measured after growth hormone therapy

S7


Table 3. Three step process Step 1: growth hormone therapy education

Step 2: device selection

Step 3: post-choice follow-up

{{ Discuss questions and concerns with parent/carer {{ Issue patient/carer with glossary of terms to understand the different features of different devices

{{ Discuss the glossary of terms with the patient/carer {{ Answer the patient’s questions on devices’ important features {{ Explain the key features of devices to the patient {{ Help the patient select a device after demonstration of those fitting identified needs {{ Provide training session with selected device

{{ Follow up with at least one home visit {{ Provide ongoing support

Source: Acerini et al (2013)

Somatotropin growth hormone molecule

S8

involvement of a dedicated clinical nurse specialist. Longer durations of growth hormone prescriptions, prescription collection and home delivery, calendars and reminders, as well as immediate and extended family and social support, can also help children and their carers to persevere with treatment. Online information, health-related technology such as mobile phone apps, patient information leaflets and support groups can educate and support patients. They can be accessed by patients and their carers at home through the internet. In the UK, an enhanced level of patient education and support is available from specialist home-care nursing teams, the majority of which are sponsored by industry to complement, when needed, the role of the paediatric endocrine nurse specialist. Such nursing teams can provide holistic care with differing levels of customised intervention based on the specific level of patient need in the community and home setting. The development and implementation of specialist nurse-led clinics, telephone support and a variety of

Laguna Design/Science Photo Library

Pasieka/Science Photo Library

hormone device is often promoted in clinical practice and the differences in growth hormone device have been extensively studied (Wickramasuriya et al, 2006; Ahmed et al, 2011). The role of the paediatric endocrine nurse specialist can be central to helping patients select the most appropriate growth hormone device to meet their requirements and to provide ongoing support during the treatment journey. Acerini et al (2012) suggested a three-step approach to improving the decision-making process for patients starting growth hormone treatment, which includes growth hormone therapy education, device selection and follow-up after making a choice (Table 3). These steps can be coordinated within the remit of the endocrine nurse specialist role. As well as giving patients a choice of injection devices, other interventions have been proposed to improve adherence with growth hormone therapy in paediatric patients. These include the use of automatic injection devices, injection pens, electronic devices, early patient or parent education and training, and the

Insulin-like growth-1 factor molecule



other initiatives, such as assessment tools, can also be used by specialist paediatric endocrine nurses to promote concordance and identify patients at risk of impaired treatment outcomes. As stated, no single intervention is likely to completely address the issue of poor adherence in patients who have difficulty maintaining treatment. Just as patients are individuals and their needs will differ, the goal of health-care professionals such as clinical nurse specialists is to provide support using a variety of interventions and evidence-based practice.

Conclusion

Growth hormone therapy has continued to develop over the past three decades. The science and technology for diagnosing growth hormone deficiency, improved understanding of abnormal growth, and development of more sophisticated and patient-friendly growth hormone devices have led to more children being treated with and benefiting from growth hormone treatment. Additional support strategies and interventions have helped children and their carers to cope with the daily demand of treatment, as the treatment period can last many years, through childhood, adolescence and, in some people, beyond the attainment of final adult height. Market forces have helped improve both the availability and accessibility of patient information and support programmes. Greater choice of growth hormone delivery devices has led to a more competitive growth hormone market in the UK. These devices have continued to evolve, with a range that meets the vast majority of patients’ needs and expectations in terms of minimising pain and discomfort, and fitting in with different lifestyles. Adherence with growth-hormone treatment often varies, and the reasons for non-adherence are multifactorial. Improved understanding by healthcare professionals and specialist paediatric nurses of this issue, combined with an awareness of the strategies that can be used to address it, can aid early detection and resolution. Regular patient contact, be it at clinic or home, and an open, cooperative and non-judgemental approach based on mutual trust can create the opportunity for patients to re-engage with treatment. However, it must be accepted that adherence is likely to remain an issue for some patients, and that, for the most part, growth hormone therapy requires a long-haul approach, with pitfalls being experienced along the way. The key to success, even with the most challenging patients, is to continue offering support and implementing strategies that can help them achieve better long-term outcomes.


References

Acerini C, Albanese A, Casey A et al (2012) Initiating growth hormone therapy for children and adolescents. Br J Nurs 21(18): 1091–7 Ahmed SF, Franey C, McDevitt H et al (2011) Recent trends and clinical features of childhood vitamin D deficiency presenting to a children’s hospital in Glasgow. Arch Dis Child 96(7): 694–06 Bissonnette JM (2008) Adherence: a concept analysis. J Adv Nurs 63(6): 634–43 Chernausek SD (2009) Management of disordered growth. In: Brook CGD, Clayton P, Brown R, eds, Brook’s Clinical Pediatric Endocrinology. 6th edn. Blackwell Publishing, Chichester, UK Dattani M, Preece M (2004) Growth hormone deficiency and related disorders: insights into causation, diagnosis, and treatment. Lancet 363(9425):1977–87 Dattani MT (2005) Growth hormone deficiency and combined pituitary hormone deficiency: does the genotype matter? Clin Endocrinol (Oxf) 63(2): 121–30 Drake AJ, Kelnar CJH (2006) The evaluation of growth and the identification of growth hormone deficiency. Arch Dis Child Educ Pract Ed 91: ep61–ep67 Fisher BG, Acerini CL (2013) Understanding the growth hormone therapy adherence paradigm: a systematic review. Horm Res Paediatr 79(4): 189–96 Haverkamp F, Gasteyger C (2011) A review of biopsychosocial strategies to prevent and overcome early-recognized poor adherence in growth hormone therapy of children. J Med Econ 14(4): 448–57 Haverkamp F, Johansson L, Dumas H et al (2008) Observations of nonadherence to recombinant human growth hormone therapy in clinical practice. Clin Ther 30(2): 307–16 Haynes RB1, Ackloo E, Sahota N, McDonald HP, Yao X (2008) Interventions for enhancing medication adherence. Cochrane Database Syst Rev (2):CD000011 Kapoor RR1, Burke SA, Sparrow SE et al (2008) Monitoring of concordance in growth hormone therapy. Arch Dis Child 93(2): 147–8 Kirk JK (2012) Indications for growth hormone therapy in children. Arch Dis Child 97(1): 63–8 Langham S, Kirk J; British Society for Paediatric Endocrinology and Diabetes (2011) National audit of patient choice in pediatric GH therapy. Horm Res Paediatr 75(2): 101–5 Lindsay R1, Feldkamp M, Harris D, Robertson J, Rallison M (1994) Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr 125(1): 29–35 National Institute for Health and Clinical Excellence (2010) Human Growth Hormone (Somatropin) for the Treatment of Growth Failure in Children (Review) (TA188). NICE, London. www.nice.org.uk/TA188 (accessed 24 February) Ranke M, Reiter EO, Price DA (2007) Idiopathic growth hormone deficiency in KIGS: selected aspects. In: Ranke M, Price DA, Reiter EO, eds, Growth Hormone Therapy in Pediatrics: 20 Years of KIGS. Karger, Basel: 116–35 Rosenfeld RG1, Bakker B (2008) Compliance and persistence in pediatric and adult patients receiving growth hormone therapy. Endocr Pract 14(2): 143–54 Stanhope R, Moyle L, MacSwiney M (1993) Patient knowledge and compliance with growth hormone treatment. Arch Dis Child 68(4): 525 Wales JK (2009) Evaluation of growth disorders. In: Brook CGD, Clayton P, Brown R, eds, Brook’s Clinical Pediatric Endocrinology. 6th edn. Blackwell Publishing, Chichester, UK Whitehead SA, Miell J (2013) The pituitary gland, chapter 2. In: Whitehead SA, Miell J, Clinical Endocrinology. Scion Publishing, Banbury Wickramasuriya BP, Casey A, Akhtar S et al (2006) Factors determining patient choice of device for GH therapy. Hom Res 65(1): 18–22 Wit JM, Karperien M, Ballieux BEPB (2009) Measuring hormones, molecular tests and their clinical application. In: Brook CGD, Clayton P, Brown R, eds, Brook’s Clinical Pediatric Endocrinology. 6th edn. Blackwell Publishing, Chichester, UK Witt JM, Ranke MB, Kelnar CJH (2007) ESPE classification of endocrine diagnoses. Hormone Research. Karger, Basel, Switzerland. https:// www.eurospe.org/journal/docs/HRE2007_068_S02_complete.pdf (accessed 24 February 2014)

S9


A strong relationship for a long journey Growth hormone treatment can take several years, which requires a high level of commitment from patients and families. Endocrine nurses need to build strong relationships with patients and their carers in order to prepare them and provide tailored, honest support Julie Jones Paediatric Endocrine Nurse, Royal Manchester Children’s Hospital

A

child/young person and caregiver starting a potentially long-term invasive therapy that involves daily injections will require a clear understanding of what the therapy entails. For some individuals, the duration of growth hormone therapy can be over 15 years and achieving the optimum outcome can involve contributions from many people. A major component in achieving this positive outcome is that the endocrine nurse specialist establishes a strong working relationship with the patient and caregiver, one with a foundation of trust to promote comfort, security and honesty. Meeting families early in their treatment journey, usually following anterior pituitary testing and confirmation that growth hormone treatment will be offered, allows the nurse to tell them about potential benefits of the treatment, and to balance this with expected and realistic outcomes. For example, when families enquire about their child’s predicted final height, a more tangible outcome is what to expect in the first year to 18 months of the treatment. It is essential that the nurse talks to the patient and caregiver about the level of commitment required from both. These conversations must include: {{ The length of the treatment {{ The rare but potential side effects, and actions to be taken if these occur {{ The importance of not missing injections. Poor adherence will jeopardise treatment efficacy and waste health-care resources (McLellan, 2009). The initial meetings with patients and families are crucial and allow the nurse to assess individual levels of coping skills. This, at times, is a somewhat intuitive nursing skill; a more concrete assessment

S10

involves identifying individual patient factors that may lessen the likelihood of growth hormone treatment being successful, i.e. the patient’s age when treatment starts, or the level of a support network. Dynamics within the home vary from family to family. Parents may be concerned that they will not be able to give an injection on their own. If the child lives between two homes because the parents are separated, the nurse may need to provide information about a growth hormone device that can be moved between them and does not need refrigeration to prevent waste. By anticipating pitfalls early, the nurse is able to tailor a solution to individual needs. Some families may need extra nurse support, in the form of homecare nurse support. Home-care nurses work in partnership with families to provide bespoke care. At all times, the endocrine nurse promotes family participation in the treatment journey. This could include sharing with them the evidence that families with low levels of conflict and high levels of cohesion and organisation are associated with a better regimen adherence (Delamater et al, 2001). Measures that families can take before starting growth hormone treatment could include discussing the planned treatment with their GP to iron out any problems. The nurse could offer organised support from a home-care company, which would order and deliver the growth hormone treatment to the home, making life a little easier and reducing trips to the GP and chemist for repeat prescriptions. The endocrine nurse also acts as a facilitator when the family is choosing which device to use. Kapoor et al (2008) identify a number of factors that influence adherence, one of which is choice of injection device. In the north west, families are provided with three choices of pen devices, one



needle free. However, this practice differs from centre to centre. The nurse should play an impartial role in the decision, but be at hand to advise about key attributes of the product, thus helping the family make a personal choice. A typical query might be that the child has a visual impairment, would like to self-inject each night and whether a device is available that would match these needs.

ing Group. Diabetes Care 24(7): 1286–92 Kapoor RR, Burke SA, Sparrow SE et al (2008) Monitoring of concordance in growth hormone therapy. Arch Dis Child 93(2): 147–8 McLellan A (2009) The nurse–patient relationship will prove key to effective medicine adherence. Nursing Times http://tinyurl.com/ o87s2kj (accessed 17 February 2014)

References

Delamater AM, Jacobson AM, Anderson B et al (2001) Psychosocial therapies in diabetes: report of the Psychosocial Therapies Work-

Case study 1. Play therapy to reduce distress Alan was three and a half years old when introduced to the endocrine nurse. His mother had concerns regarding his growth since around his second birthday and saw that his twin sister was noticeably taller. Alongside family concerns about his height, Alan’s mother was worried about his obsessive behaviour, such as his repetitive play with his toys, and at times the expression of high levels of anxiety and distress in response to situations at home, such as being unable to cope with slight changes in routine. After being advised that Alan should start growth hormone treatment, Alan’s mother feared this new event would affect his behaviour. In the past, Alan had been supported by a play therapist in the hospital during blood testing. He had responded well to distraction techniques such as blowing bubbles during blood testing, as well as to play therapy that involved dressing up and acting out situations, such as taking blood from dolls. Alan enjoyed playing with dinosaurs and, before starting growth hormone treatment, the same play therapist visited the family at home and used puppetry and a dinosaur book to discuss future treatment. The dinosaur in the book had an injection every day and grew from a baby into an adult dinosaur. Using the actual medical device, Alan played at giving his toy dinosaur an injection; pictures were taken of this process and a scrapbook was devised. The next visits involved the device being placed on Alan’s leg, and reward stickers put on the device and


iStock/ooyoo

Julie Jones Paediatric Endocrine Nurse, Royal Manchester Children’s Hospital

in the book. Over a 4-week period, which included several joint visits from the play specialist and the endocrine nurse, his mother felt confident to try the actual injection. Ice packs had also been used during the period of play therapy and explanations were given to the child on how this would help with the pain. The first week of injections was difficult as Alan became distressed; however, his mother felt confident enough to continue with the injection. She reported that maintaining a strict daily routine, giving the injection at a similar time, also helped in the early months of the treatment.

Get input from other specialties and manage pain

The input from another specialty was vital for Alan. They recognised the level of stress and anxiety that starting growth hormone treatment could cause. Thanks to a mixture of distraction and play therapy, daily injections became part of Alan’s daily routine. Tolerating pain is an individual concept. Using pain-management techniques can aid with the daily injections. Ice-pack therapy prior to the injection is cheap, tolerable and usually a short-term aid. Families report that pen devices with an autoinjector facility or a needle guard aid administration of injections.

S11


Case study 2. Empowering patients and caregivers around their condition Julie Jones Paediatric Endocrine Nurse, Royal Manchester Children’s Hospital Brian started his daily injections at 14 years, after recent debulking surgery for a craniopharyngioma resulted in panhypopituitarism. His parents had a good understanding of replacement medication, such as thyroxine and hydrocortisone, and now wanted to extend their knowledge further by learning more about growth hormone treatment. Written, verbal and visual information in the form of growth hormone DVDs and actual devices were provided to Brian and his family. This covered what the treatment entailed, how injections were administered,

what devices were available to meet his needs, how and why the treatment was assessed using IGF-1 monitoring, as well as the rare side effects of treatment and what actions to take if symptoms occurred. The key elements of patient empowerment are knowledge, good behavioural skills and selfresponsibility. Brian benefited from this targeted approach, whereby specific information was selected to meet his and his parents’ needs. He gained a good understanding of his condition, achieving a good growth response.

Case study 3: Resistance to adherence Deborah Slater Nurse Manager, Ipsen Homezone Nurse Team, Ashfield Healthcare would like this. This initial phone call is the first stage in engaging with a family. We agreed to meet the following day after school. On arriving at the home, I was welcomed warmly, but quickly sensed feelings of anxiety from both mother and daughter—Claire was standing and moving from foot to foot quickly, and Abi was pushing herself into the back of the settee with her knees pulled into her body. The mother was keen to ‘get on’ quickly with the injection; however, I explained that we needed to have a chat first, and would discuss the injection in a little while. I then went over how I could support the family, provided written information and, most importantly, gave Abi and Claire the reassurance that the visit was not a ‘one off’, but that support was provided on an individual basis, according to each family’s need. We then chatted over a cup of tea about Abi’s referral to her specialist team. I have found it important to allow parents time to reflect over the process, and going over the history can help parents gain clarity regarding the prescribed treatment. In their own home, they can do this in a relaxed atmosphere without thinking they are taking up too much time in clinic. Furthermore, as I explain that I haven’t seen the child’s hospital notes, it allows them to go through their child’s history from the beginning, mentioning matters that may be particularly important to them. This can allow them to explore feelings and anxieties about the treatment.

iStock/aluxum

I am sponsored by a pharmaceutical company to provide education and teaching about a growth hormone product and to deliver a device to patients and their families, in their own homes, after it has been prescribed by their specialist paediatric team. Abi, aged 7 years, was referred to the service by her specialist nurse (SN), as she was refusing injections from her mother, Claire. The SN also outlined the nature of Abi’s refusal in a telephone call. I contacted Claire and gave her an outline of my role and how I could support both her and Abi, if she

S12



I have found that this process often enables the family to gain clarity around their child’s condition and the consequences of non-adherence, and therefore take ownership of the treatment. Abi was included in the conversation in an age-appropriate way, which encouraged her to relax and accept me as a visitor to her home. Her mother is a single parent and highly motivated to administer the injections she knew were necessary for her daughter. It was apparent that she wanted and expected everything to be ‘perfect’. The relationship with her daughter was understandably very close, with mother and daughter often referring to themselves as ‘the team’. They had a very loving relationship, but it seemed as though this ‘equal’ relationship was contributing to Abi’s refusal of her injections, with Claire’s insistence and Abi’s refusal contributing to the escalating anxiety at injection time. By this stage, the two were far more relaxed and Abi wanted to show me some of her special toys. When Abi went upstairs to collect them, I discussed with her mother the need for her to take the lead by making it clear to Abi that she was in control; this would give Abi a sense of security at injection time. I checked that the medication was being stored correctly, and explained that this would keep it effective. I reviewed Claire’s technique with the pen device so she would be confident that she was administering the medication correctly. We discussed options for areas of the body that could be used for injection. We then talked about ways that Claire could hold Abi while giving the injection, which would ensure that she remained still while reinforcing a feeling of safety and security. I was fully aware that all these issues would have been discussed with her SN; however, Claire would have had to take in and understand a lot of new information at a time of anxiety. Going through this again allowed Claire the opportunity ask about anything she had not understood, and to express what she did understand. She was therefore able to take ownership of the treatment and this contributed to her sense of confidence.

The injection was then administered by Claire, with me providing reassurance to both. Abi did cry during the injection, but Claire was able to keep her still and carry out the injection safely. Abi was quickly pacified, then distracted by a cuddle and completing her sticker chart, which had been provided by her SN. I reassured Claire that crying at this level was a completely normal reaction to fear of the injection and its associated discomfort, and to be expected at Abi’s age and developmental stage. We then made arrangements for me to visit again the following evening. Claire had taken the medication out of the fridge before the visit so, after a quick welcome, she put into practice the routine of the evening before, this time with only brief information to Abi, rather than protracted explanations and reasons. Again, Abi soon recovered with a cuddle and the sticker chart. We then agreed that Claire would follow the same routine the following evening, and I would visit after the weekend. The following week, I visited on alternate days, with Claire becoming increasingly more confident and Abi more accepting. Visits were gradually reduced, with telephone contact in between to maintain support. Once the original sticker chart had been completed, I provided another more tailored chart, as this appeared to motivate Abi. It is now some months since I first visited, and Abi’s mother reports adherence with the therapy. Feedback from the SN is that Abi has grown significantly, and Abi says that she can now reach the bottom of the pool during swimming lessons. We maintain telephone support and Claire is aware that a visit can be arranged if needed, as adherence can be affected at any time during treatment. In conclusion, by using a holistic, family-focused approach, a routine has been established for this child to optimise the likelihood of adherence with therapy. Another family may require a different approach. By working in a non-judgemental partnership with the family, nurses can have a significant effect on the experience of children requiring growth hormone therapy, and therefore on their treatment outcome.

Case study 4: When adherence is a struggle Lee Martin Clinical Nurse Specialist, Paediatric Endocrinology, Barts Health NHS Trust In 2004, aged four and a half years, Jane was diagnosed with idiopathic growth hormone deficiency following a growth hormone stimulaton test. She measured 85.6 cm in height, which was 4.1 standard deviations (SDs) below the norm for her age and sex.


After the diagnosis, a paediatric endocrine nurse specialist (PENS) discussed the various growth hormone delivery devices with Jane and her mother. The nurse demonstrated how to use each device, and Jane’s mother then had the opportunity to deliver a

S13


Figure 1. Jane’s growth chart placebo into an injection pad. The PENS, Jane and her mother also discussed in detail what having a daily growth hormone injection would involve. They chose an easy-to-assemble pen device with a smooth delivery button, digital dose display and changeable pen cover, which allowed Jane to personalise it. Next, the PENS signed up Jane and her mother for training on the device, which was to be delivered by the home-care nurse. Jane opted for a needle guard so she would not see the needle, as well as a sticker chart, onto which she would place a sticker for each successful injection, with the prospect of a reward for a full set of stickers at the end of each month. For the first 3 years, Jane was assessed every 4–6 months in the hospital’s growth clinic. She made excellent progress and, by the age of 7.5 years, had reached 110.8 cm and was now only 2.1 SDs below the norm for her age and sex. However, maintaining long-term adherence with treatment was starting to prove difficult. As Jane got older, she became less cooperative with treatment and her mother was finding it more challenging to give the injections. Jane’s growth chart showed that she only grew 4.8 cm over the next 3 years. During this stage, the PENS explored the issues relating to this with Jane and her mother, and a number of strategies were introduced to help them achieve better outcomes. A growth chart is a good tool to help children/young people and their families understand how successful their treatment is. Jane’s growth chart (Figure 1) clearly shows when she was and was not concordant with her treatment. Its use also led to discussion,

S14

when needed, on the need for the treatment and why good adherence was necessary. It is important to note that cost was broached with Jane’s mother. Growth hormone therapy is extremely expensive; parents need to appreciate that if their child does not receive regular injections, this not only will adversely affect his/her final height, but also is an ineffective use of finite NHS resources. Jane was encouraged to get more involved with her treatment, for example, by choosing where to have her injection, helping her mother to dial up the dose, and by putting the pen away after the injection. The reward system was reintroduced as it had not been used after the first couple of years. However, these measures had only limited success on Jane’s adherence with treatment. As a result, the PENS, in collaboration with Jane and her mother, decided to change to a needleless device that used pressure to administer the growth hormone transdermally. Unfortunately, this had a limited impact as the family struggled with both the extra number of steps involved in this process and the noise the device made during application. Even though Jane and her mother became even more despondent with this device, they persisted with it for a number of months. The PENS then decided to steer them towards another device—a disposable pen that requires very few steps to prepare and, unlike other brands, does not need to be stored in the fridge. A key factor influencing this decision is that a home nurse service is available to support families using this device with home visits. The device was so simple to use that Jane was able to do her own injections, with the support of regular home visits from the home nurse service. While this new treatment journey has not been without its problems, both Jane and her mother have continued to engage with the home nurse service and, in particular, the PENS. No doubt, empowering Jane to give her own injections, along with the extra support from the home nurse service and more frequent visits to see the PENS in the growth clinic, have contributed to her improved adherence. Through open dialogue and good communication, a relationship of trust and confidence was established. This allowed the PENS to uncover the issues around poor adherence and instigate both support and alternative treatment systems. Jane is now 13. Her adherence is still not perfect as she still misses, on average, one injection each week. However, she is receiving much more of her treatment than before and showing excellent catch-up growth, having grown 5 cm in the past 6 months. All names have been changed throughout these case studies



Treating Turner syndrome: a patient’s perspective Here, teenager Faye Hirons describes her patient journey over 10 years on growth hormone therapy, the support she received from practitioners and family, and how monitoring her height motivated her to persevere with the treatment

I

am a 16-year-old girl and was diagnosed with Turner syndrome when I was 5 years old, so I have lived with Turner syndrome for the majority of my life. However, it really wasn’t until the past few years that I started to learn more in depth about this syndrome, what the medication did to me and what caused me to have Turner syndrome. When I started primary school, my parents noticed that I was shorter than many of my schoolfriends. This led to my parents taking me to the doctor to try to see why. I had a simple blood test and they diagnosed me with Turner syndrome. From then on, I have not been treated differently and have had the best treatment that could be offered. I have felt I could always speak to the doctors about anything and they were always there to help me, even more so as my body was changing as I was going through my early teens. I have had to have injections 6 days a week, every week, since I was diagnosed. This was very hard for me and my parents in the beginning but, like with most things, you get used to it. Like most people, I do not like needles. This meant that my mum and dad had to inject me in my thighs for many years until I was old enough to do it myself. They always talked about what they were doing and why, but it was not until I was much older that I fully understood. I overcame my fear of needles so, throughout the years, it got easier. I learned about what my growth hormone therapy did after it was injected into my body. When I visited the specialist clinic in London for a check-up, I had a nurse who always weighed me and measured my height. Then he plotted the chart, showing average heights of girls, then showing me where I was. My parents and I quickly became aware of how this medication was working and how quickly I reacted to it. I was lucky enough not to be too far below the average Turner line on the chart. I had a goal; this kept me going, knowing that whenever I had


the injection it would help me grow, so I could reach the average line for my age. Once I started injecting myself on my own, by the age of 9, I was so very proud of myself and I knew what we were doing. I have finished taking the injections now, which was very sad because then I knew I was never going to grow that much more. However, I managed to reach my goal and get to the average height of a Turner girl, which was something that really pleased me, especially given the fact that my parents aren’t exactly the tallest people. I think I fit in pretty well.

S15


Growth hormone therapy in children with chronic renal failure.

Growth and growth hormone therapy in hypochondroplasia.

Altered growth hormone response after growth hormone releasing hormone administration in chronic renal failure.

Growth hormone therapy in achondroplasia.

Hormone replacement therapy in heart failure.

Growth hormone replacement therapy and fracture risk.

Accelerated growth in short children with chronic renal failure treated with both strict dietary therapy and recombinant growth hormone.

Diagnostic significance of urinary growth hormone measurements in children with growth failure: correlation between serum and urine growth hormone.

Pituitary size and response of growth hormone deficient children to growth hormone therapy.

Growth hormone during catch-up growth and failure of catch-up growth in rats.

Growth hormone therapy in elderly people.

Growth hormone replacement therapy in Costello syndrome.

Effect of Growth hormone replacement therapy on soluble Klotho in patients with Growth hormone deficiency.

Efficacy of growth hormone therapy in adults with childhood-onset growth hormone deficiency.

Growth hormone binding protein in patients with renal failure.

Toward gene therapy for growth hormone deficiency via salivary gland expression of growth hormone.

Failure of growth hormone-suppressing agents to affect TSH-releasing hormone- and LH-releasing hormone-induced growth hormone release in acromegaly.

Psychosocial growth failure: a positive response to growth hormone and placebo.

Growth hormone treatment of growth failure secondary to total body irradiation and bone marrow transplantation.

Human growth hormone replacement therapy: pharmacological and clinical aspects.

Growth hormone therapy for Prader-willi syndrome: challenges and solutions.

Growth hormone therapy in normal short children induces a transitory decrease in plasma growth hormone releasing hormone levels and in human growth hormone responsiveness to exogenous growth hormone releasing hormone.

Response to growth hormone-releasing hormone in adult renal failure patients on hemodialysis.

Long-term failure of compensatory growth in rats following acute neonatal passive immunization against growth hormone-releasing hormone.